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1.  A comparison of migrants to, and women born in, urban Mongolia: demographic, reproductive, anthropometric and lifestyle characteristics 
International Health  2013;5(4):244-250.
Mongolia has experienced vast migration from rural to urban areas since the 1950s. We hypothesized that women migrating to Ulaanbaatar, the capital, would differ in factors related to future chronic disease risk compared with women who were born in Ulaanbaatar.
Premenopausal mothers (aged <44 years) of children attending two schools (one in the city centre and one in the outskirts) in Ulaanbaatar were recruited for the study. During April and May 2009, 420 women were interviewed about migration, reproductive history and lifestyle factors and anthropometric measurements were taken.
Women born in (n=178) and outside (n=242) Ulaanbaatar were similar in education and marital status, but the latter appeared to have a more traditional lifestyle including being more likely to have lived as a nomadic herder (22.3% vs 5.6%; p<0.001) and to currently live in a traditional yurt or ger (40.1% vs 29.2%). Ever-use of hormonal contraception was more common in women born outside Ulaanbaatar (52.1% vs 38.2%; p=0.005) and their age at first live birth was older (26.0% vs 20.8% for ≥25 vs <25 years). Although the number of pregnancies was similar, the number of live births was greater for those born outside Ulaanbaatar (p=0.002). Women born in Ulaanbaatar were more likely to have smoked cigarettes (24.7% vs 11.2%; p<0.001). Women born outside Ulaanbaatar were more likely to consume the traditional meat and dairy diet.
Rural migrants to Mongolia's capital have retained a traditional lifestyle in some, but not all, respects. Internal migrant populations may provide the opportunity to assess the effect of changes in isolated risk factors for subsequent chronic disease.
PMCID: PMC3850362  PMID: 24021762
Lifestyle; Reproductive factors; Diet; Non-communicable diseases; Mongolia; Asia
2.  Pregnancy-related Characteristics and Breast Cancer Risk 
Cancer causes & control : CCC  2013;24(9):1675-1685.
Breast tissues undergo extensive physiologic changes during pregnancy, which may affect breast carcinogenesis. Gestational hypertension, pre-eclampsia/eclampsia, gestational diabetes, pregnancy weight gain, and nausea and vomiting (N&V) during pregnancy may be indicative of altered hormonal and metabolic profiles and could impact breast cancer risk. Here, we examined associations between these characteristics of a woman’s pregnancy and her subsequent breast cancer risk. Participants were parous women that were recruited to a population-based case-control study (Western New York Exposures and Breast Cancer Study). Cases (n=960), aged 35-79 years, had incident, primary, histologically-confirmed breast cancer. Controls (n=1,852) were randomly selected from Motor Vehicle records (<65 years) or Medicare rolls (≥65 years). Women were queried on their lifetime pregnancy experiences. Multivariable-adjusted logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). N&V during pregnancy was inversely associated with breast cancer risk. Relative to those who never experienced N&V, ever experiencing N&V was associated with decreased risk (OR 0.69, 95% CI: 0.56-0.84) as were increased N&V severity (P-trend<0.001), longer duration (P-trend<0.01), and larger proportion of affected pregnancies (P-trend<0.0001) among women with ≥3 pregnancies. Associations were stronger for more recent pregnancies (<5y). Findings did not differ by menopausal status or breast cancer subtype including estrogen receptor and HER2 expression status. Other pregnancy characteristics examined were not associated with risk. We observed strong inverse associations between pregnancy N&V and breast cancer risk. Replication of these findings and exploration of underlying mechanisms could provide important insight into breast cancer etiology and prevention.
PMCID: PMC3737361  PMID: 23737027
gestational hypertension; gestational diabetes; nausea; pre-eclampsia; pregnancy weight gain; vomiting
3.  Invited Commentary: Are Dietary Intakes and Other Exposures in Childhood and Adolescence Important for Adult Cancers? 
American Journal of Epidemiology  2013;178(2):184-189.
In this issue of the Journal, Nimptsch et al. (Am J Epidemiol. 2013;178(2):172–183) report significant associations between female adolescents' poultry consumption in high school and subsequent reduced risk of colorectal adenomas in adulthood. Consumption of red meat or fish was not related to risk, but replacement with poultry reduced the risk of later adenomas. Most epidemiologic studies of adult diseases lack exposure data from the distant past. By focusing on a cancer precursor lesion and using a variety of methods to assess data quality, the investigators address concerns about the quality of distant recall. These findings add to the growing evidence that links childhood and adolescent lifestyle and environmental exposures with subsequent risk of cancers arising in adulthood. Highlights of the literature on this topic and methodological challenges are summarized. Future studies would benefit from incorporating measures of lifestyle, diet, environmental exposures, and other risk factors from early in life and from validation and other data quality checks of such measurements. Sources of historical data on children's and adolescents' exposures should be sought and evaluated in conjunction with subsequent exposures in relationship to adult-onset cancers.
PMCID: PMC3816339  PMID: 23792894
adolescence; diet; distant past; life course; methods; recall
4.  Behavior and food consumption pattern of the population exposed in 1949–1962 to fallout from Semipalatinsk nuclear test site in Kazakhstan 
Radiation and environmental biophysics  2010;50(1):10.1007/s00411-010-0334-9.
The relationship between radiation exposure from nuclear weapons testing fallout and thyroid disease in a group of 2,994 subjects has been the subject of study by the U.S. National Cancer Institute. In that study, radiation doses to the thyroid were estimated for residents of villages in Kazakhstan possibly exposed to deposition of radioactive fallout from nuclear testing conducted by the Soviet Union at the Semipalatinsk Nuclear Test Site in Kazakhstan between 1949 and 1962. The study subjects included individuals of both Kazakh and Russian origin who were exposed during childhood and adolescence. An initial dose reconstruction used for the risk analysis of Land et al. (2008) was based on individual information collected from basic questionnaires administered to the study population in 1998. However, because data on several key questions for accurately estimating doses was not obtained from the 1998 questionnaires it was decided to conduct a second data collection campaign in 2007. Due to the many years elapsed since exposure, a well developed strategy was necessary to encourage accurate memory recall. In our recent study, a focus group interview data collection methodology was used to collect historical behavioral and food consumption data. The data collection in 2007 involved interviews conducted within four eight-person focus groups (three groups of women and one group of men) in each of four exposed villages where thyroid disease screening was conducted in 1998. Population-based data on relevant childhood behaviors, including time spent in- and outdoors and consumption rates of milk and other dairy products were collected from women’s groups. The data were collected for five age groups of children and adolescents ranging from less than 1 year of age to 21 years of age. Dairy products considered included fresh milk and other products from cows, goats, mares, and sheep. Men’s focus group interviews pertained to construction materials of houses and schools, and animal grazing patterns and feeding practices. The response data collected are useful for improving estimates of thyroid radiation dose estimates for the subjects of an ongoing epidemiological study.
PMCID: PMC3853382  PMID: 20938673
5.  The Utility of Focus Group Interviews to Capture Dietary Consumption Data in the Distant Past: Dairy Consumption in Kazakhstan Villages 50 Years Ago 
Journal of developmental origins of health and disease  2010;1(3):10.1017/S2040174410000243.
From 1949 to 1962, residents of several villages in Kazakhstan Abstract: received substantial doses of radiation to the thyroid gland resulting from nuclear tests conducted at the Semipalatinsk Nuclear Test Site. The primary source of radiation was internal from an intake of radioactive iodine by consumption of contaminated dairy products. A previous research study of childhood exposure and thyroid disease in this region gathered limited data on study participants’ dairy intake at the time of the fallout for the purpose of estimating past radiation doses. Because many subjects were too young at the time of the nuclear tests to recall dietary consumption and existing sources of archival data are limited, it was necessary to interview parents and other village residents who cared for children during this time; older adults ranging in age from 75 to 90 years old. Results from 11 focus group interviews conducted in 2007 with 82 women from 4 villages in Kazakhstan yielded group-level estimates of age-, gender-, ethnicity- and village-specific dairy consumption patterns in rural Kazakhstan during the 1950s. Children typically consumed cow’s milk with limited consumption of mare, goat, and sheep milk; and consumed dairy products such as sour milk (airan), soft cottage cheese (tvorog), and fermented mare milk (koumiss) with the greatest amounts of koumiss reported at ages 15–21. The consumption patterns differed by age and between Kazakh and Russian children, which should lead to different estimates of radiation exposure to the thyroid. This study demonstrated the utility of focus groups to obtain quantitative estimates for dietary intake in the distant past.
PMCID: PMC3839237  PMID: 24286002
6.  Assessment of the Accuracy of Portion Size Reports Using Computer-Based Food Photographs Aids in the Development of an Automated Self-Administered 24-Hour Recall 
To assess the accuracy of portion-size estimates and participant preferences using various presentations of digital images.
Two observational feeding studies were conducted. In both, each participant selected and consumed foods for breakfast and lunch, buffet style, serving themselves portions of nine foods representing five forms (eg, amorphous, pieces). Serving containers were weighed unobtrusively before and after selection as was plate waste. The next day, participants used a computer software program to select photographs representing portion sizes of foods consumed the previous day. Preference information was also collected. In Study 1 (n=29), participants were presented with four different types of images (aerial photographs, angled photographs, images of mounds, and household measures) and two types of screen presentations (simultaneous images vs an empty plate that filled with images of food portions when clicked). In Study 2 (n=20), images were presented in two ways that varied by size (large vs small) and number (4 vs 8).
Convenience sample of volunteers of varying background in an office setting.
Statistical analyses performed
Repeated-measures analysis of variance of absolute differences between actual and reported portions sizes by presentation methods.
Accuracy results were largely not statistically significant, indicating that no one image type was most accurate. Accuracy results indicated the use of eight vs four images was more accurate. Strong participant preferences supported presenting simultaneous vs sequential images.
These findings support the use of aerial photographs in the automated self-administered 24-hour recall. For some food forms, images of mounds or household measures are as accurate as images of food and, therefore, are a cost-effective alternative to photographs of foods.
PMCID: PMC3773715  PMID: 20102828
8.  Reactivity and its association with body mass index across days on food checklists 
Characterizing relationships between diet, body weight, and health is complicated by reporting errors in dietary intake data that are associated with body weight. The objectives of this study were to assess changes in reporting across days (reactivity) on food checklists and associations between reactivity and body mass index (BMI) using data from two cross-sectional studies: 1) the Recontacting Participants in the Observing Protein and Energy Nutrition study (n = 297), which was conducted in 2003–2004 and included a 7-day checklist and a 4-day food record (FR), and 2) the America’s Menu Daily Food Report Study (n=530), which was conducted in 1996 and included a 30-day checklist. Zero-inflated Poisson regression was used to assess effects of reporting day on frequency of consumption for the checklists and number of items reported for the FR. Interactions between day and BMI were tested using contrast statements. Frequency of reported consumption declined across days among males and females for total items and many of the eight food groups on the 7-day checklist; among females, the effect of reporting day differed by BMI category for the meat, fish, and poultry group. Smaller declines across days were observed for some of the 22 food groups on the 30-day checklist; no interactions with BMI were apparent. No reporting day effects were observed in the FR data. The results suggest inconsistent reactivity across days, possibly reflecting changes in reporting or consumption behavior. However, the effects are generally small and independent of body weight, suggesting that checklists are potentially useful for the study of body weight and diet.
PMCID: PMC3269781  PMID: 22308230
dietary assessment; food checklist; measurement error; reactivity; body mass index; obesity
9.  Using Regression Calibration Equations That Combine Self-Reported Intake and Biomarker Measures to Obtain Unbiased Estimates and More Powerful Tests of Dietary Associations 
American Journal of Epidemiology  2011;174(11):1238-1245.
The authors describe a statistical method of combining self-reports and biomarkers that, with adequate control for confounding, will provide nearly unbiased estimates of diet-disease associations and a valid test of the null hypothesis of no association. The method is based on regression calibration. In cases in which the diet-disease association is mediated by the biomarker, the association needs to be estimated as the total dietary effect in a mediation model. However, the hypothesis of no association is best tested through a marginal model that includes as the exposure the regression calibration-estimated intake but not the biomarker. The authors illustrate the method with data from the Carotenoids and Age-Related Eye Disease Study (2001--2004) and show that inclusion of the biomarker in the regression calibration-estimated intake increases the statistical power. This development sheds light on previous analyses of diet-disease associations reported in the literature.
PMCID: PMC3224252  PMID: 22047826
bias (epidemiology); carotenoids; cataract; lutein; measurement error; sample size
10.  Sugars in diet and risk of cancer in the NIH-AARP Diet and Health Study 
Prospective epidemiologic data on the effects of different types of dietary sugars on cancer incidence have been limited. In this report, we investigated the association of total sugars, sucrose, fructose, added sugars, added sucrose and added fructose in the diet with risk of 24 malignancies. Participants (n = 435,674) aged 50–71 years from the NIH-AARP Diet and Health Study were followed for 7.2 years. The intake of individual sugars was assessed using a 124-item food frequency questionnaire (FFQ). Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) in multivariable models adjusted for confounding factors pertinent to individual cancers. We identified 29,099 cancer cases in men and 13,355 cases in women. In gender-combined analyses, added sugars were positively associated with risk of esophageal adenocarcinoma (HRQ5 vs. Q1: 1.62, 95% CI: 1.07–2.45; Ptrend = 0.01); added fructose was associated with risk of small intestine cancer (HRQ5 vs. Q1: 2.20, 95% CI: 1.16–4.16; Ptrend = 0.009); and all investigated sugars were associated with increased risk of pleural cancer. In women, all investigated sugars were inversely associated with ovarian cancer. We found no association between dietary sugars and risk of colorectal or any other major cancer. Measurement error in FFQ-reported dietary sugars may have limited our ability to obtain more conclusive findings. Statistically significant associations observed for the rare cancers are of interest and warrant further investigation.
PMCID: PMC3494407  PMID: 21328345
Sugars; added sugars; diet; cancer; AARP Study
11.  Maternal Angiogenic Profile in Pregnancies that Remain Normotensive 
We sought to determine if maternal characteristics are associated with angiogenic profile in the first and second trimester of normotensive pregnancies.
Study Design
Circulating levels of maternal placental like growth factor (PlGF), soluble fms-like tyrosine kinase receptor (sFlt1), and soluble endoglin (sEng) were measured in serum samples collected during the first (median 11.3 weeks) and second trimester (median 17.1 weeks) of 182 normotensive pregnancies. Diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP) were measured at the same visits when samples were collected to measure angiogenic factors. Linear regression analysis was used to examine associations of the angiogenic measures with maternal characteristics. The association between blood pressure measures and concentrations of angiogenic factors was evaluated using Spearman correlation and linear regression analysis.
In adjusted analyses, nulliparous women had higher sFlt1 concentrations in both first (P=0.06) and second (P=0.001) trimester. Higher BMI was associated with greater sFlt1 concentrations in both the first (P=0.004) and second trimester (P=0.008), but significantly lower sEng concentrations in both trimesters (P=0.002 for first trimester and P=0.0009 for second). Nulliparity and higher BMI also were associated with higher sFlt1/PLGF anti-angiogenic ratios in both first (p=0.05 and p=0.007, respectively) and second trimesters (p=0.003 and p=0.02, respectively). First trimester sFlt1 levels were weakly correlated with first trimester SBP (rs=0.18, p=0.03) and MAP (rs=0.16, p=0.04). Second trimester sEng levels were inversely associated with second trimester MAP (rs= −0.17, p=0.05). Including blood pressure measures in the linear regression models did not change the reported associations of angiogenic factors with maternal characteristics.
These results demonstrate that even early in normotensive pregnancies maternal characteristics are associated with variations in angiogenic profile across this population.
PMCID: PMC3302581  PMID: 21641103
Pregnancy; angiogenic factors; sFlt1; PlGF; soluble endoglin; maternal
12.  Association of serum sex steroid hormone hemodilution and body mass index among healthy postmenopausal women 
Annals of epidemiology  2011;21(6):466-471.
Hemodilution refers to reduced concentrations of analytes in the blood secondary to increased fluid volume. Given that obesity is associated with expanded vascular volume, hemodilution may result in a lower ratio of blood concentrations of analytes among heavier subjects. Assessing the relationship of hormone concentration to total mass varies by body mass index (BMI) is etiologically important because obesity is related to hormone metabolism and cancer risk.
We evaluated data for 194 postmenopausal controls in an endometrial cancer case-control study. Height, weight, and serum hormone concentrations were measured previously. We estimated serum hormone mass from concentration based on estimates of calculated plasma volume. We assessed the effect of BMI on relationships of sex steroid hormone concentration and mass using multivariate linear regression.
Higher BMI was associated with increased estrone, estrone sulfate, estradiol, and albumin-bound estradiol concentrations and masses (p-trend <0.001). With increasing BMI, androstenedione concentration did not change significantly (p-trend=0.548), but its mass increased (p-trend=0.024).
Relationships of sex steroid hormone concentration and mass were generally similar, except for androstenedione in which the relationship was only significant for mass. Future studies to assess both sex steroid hormone concentration and mass may have value in etiological research.
PMCID: PMC3090465  PMID: 21435901
sex steroid hormones; obesity; hemodilution
13.  Challenges in converting an interviewer-administered food probe database to self-administration in the National Cancer Institute Automated Self-administered 24-Hour Recall (ASA24) 
The National Cancer Institute (NCI) is developing an automated, self-administered 24-hour dietary recall (ASA24) application to collect and code dietary intake data. The goal of the ASA24 development is to create a web-based dietary interview based on the US Department of Agriculture (USDA) Automated Multiple Pass Method (AMPM) instrument currently used in the National Health and Nutrition Examination Survey (NHANES). The ASA24 food list, detail probes, and portion probes were drawn from the AMPM instrument; portion-size pictures from Baylor College of Medicine’s Food Intake Recording Software System (FIRSSt) were added; and the food code/portion code assignments were linked to the USDA Food and Nutrient Database for Dietary Studies (FNDDS). The requirements that the interview be self-administered and fully auto-coded presented several challenges as the AMPM probes and responses were linked with the FNDDS food codes and portion pictures. This linking was accomplished through a “food pathway,” or the sequence of steps that leads from a respondent’s initial food selection, through the AMPM probes and portion pictures, to the point at which a food code and gram weight portion size are assigned. The ASA24 interview database that accomplishes this contains more than 1,100 food probes and more than 2 million food pathways and will include about 10,000 pictures of individual foods depicting up to 8 portion sizes per food. The ASA24 will make the administration of multiple days of recalls in large-scale studies economical and feasible.
PMCID: PMC2786178  PMID: 20161418
National Health and Nutrition Examination Survey; NHANES; 24-hour recall; Self-administered 24-hour dietary recall; ASA24; Food portion photograph; AMPM interview; Food data management
14.  Anthropometric Correlates of Insulin-Like Growth Factor 1 (IGF-1) and IGF Binding Protein-3 (IGFBP-3) Levels by Race/Ethnicity and Gender 
Annals of epidemiology  2009;19(12):841-849.
Insulin-like growth factor 1 (IGF-1) levels are positively related to some cancers and negatively related to cardiovascular disease. These conditions are also related to insulin resistance and high body weight leading to the hypothesis that IGF-1 levels may, in part, mediate the association of high body weight with these health outcomes. Using the National Health and Nutrition Examination Survey (NHANES) III population, we examined the associations between IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 molar ratio with anthropometric measures in a large, United States population-based study where these associations could also be stratified by race/ethnicity and gender.
The study population consisted of 3168 women and 2635 men (44% non-Hispanic white, 28.2% non-Hispanic black and 27.7% Mexican-American). Anthropometric measures were obtained by trained personnel in the NHANES mobile examination centers. IGF-1 and IGFBP-3 were measured using immunoassays by staff at Diagnostic System Laboratories (DSL) Inc. (Webster, TX). Associations of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio with anthropometric variables across race/ethnicity and gender were evaluated using linear regression modeling.
Body mass index (BMI) was inversely associated with IGF-1 levels across all of the race/ethnicity and gender subgroups. In contrast, BMI, waist:hip ratio (WHR), and waist circumference were positively associated with IGFBP-3 levels only in non-Hispanic black men and non-Hispanic white women. The IGF-1/IGFBP-3 molar ratio was inversely associated with all anthropometric measures, except height, in all subgroups of the population.
The significant inverse associations of BMI with IGF-1 levels and of all anthropometric variables, except height, with the IGF-1:IGFBP-3 molar ratio in all subgroups do not support existing hypotheses that associations of excess weight with negative health outcomes, such as specific cancer diagnoses, are mediated through high IGF-1 levels.
PMCID: PMC2786816  PMID: 19944347
BMI; obesity; cancer; IGF
15.  Gains in Statistical Power From Using a Dietary Biomarker in Combination With Self-reported Intake to Strengthen the Analysis of a Diet-Disease Association: An Example From CAREDS 
American Journal of Epidemiology  2010;172(7):836-842.
A major problem in detecting diet-disease associations in nutritional cohort studies is measurement error in self-reported intakes, which causes loss of statistical power. The authors propose using biomarkers correlated with dietary intake to strengthen analyses of diet-disease hypotheses and to increase statistical power. They consider combining self-reported intakes and biomarker levels using principal components or a sum of ranks and relating the combined measure to disease in conventional regression analyses. They illustrate their method in a study of the inverse association of dietary lutein plus zeaxanthin with nuclear cataracts, using serum lutein plus zeaxanthin as the biomarker, with data from the Carotenoids in Age-Related Eye Disease Study (United States, 2001–2004). This example demonstrates that the combined measure provides higher statistical significance than the dietary measure or the serum measure alone, and it potentially provides sample savings of 8%–53% over analysis with dietary intake alone and of 6%–48% over analysis with serum level alone, depending on the definition of the outcome variable and the choice of confounders entered into the regression model. The authors conclude that combining appropriate biomarkers with dietary data in a cohort can strengthen the investigation of diet-disease associations by increasing the statistical power to detect them.
PMCID: PMC2945826  PMID: 20716705
carotenoids; cataract; lutein; ranks; sample size
16.  Race/ethnic Variation in Serum Levels of IGF-I and IGFBP-3 in US Adults 
The IGF axis plays a significant role in normal growth and development and variation in IGFs is associated with health outcomes. Past studies report variation in IGF levels among race/ethnic groups known to differ in disease incidence. This paper reports on race/ethnic variation in serum levels of IGF-I and IGF-BP3 in a nationally representative and ethnically diverse sample of US adults.
Serum IGF-I and IGFBP-3 levels from the fasting subsample (n = 6061) of respondents to the US National Health and Nutrition Examination Survey III (NHANES III) were analyzed using an IGF-I ELISA (Diagnostic Systems Laboratory (DSL) 10–5600) and an IGFBP-3 IRMA (DSL 6600). The NHANES is a combined examination and interview survey of a nationally representative sample of US adults. Regression analyses were used to estimate cross-sectional associations between the IGF axis and demographic variables.
In unadjusted analyses, serum IGF-I levels were higher in males than in females, and IGFBP-3 levels were higher in females than in males. Both analytes were lower in older adults. Univariate analyses indicate that serum levels of IGF-I are lower in female Non-Hispanic Whites (NHW) (256 [4.9]) and Hispanics (249 [6.6]) than in Non-Hispanic Blacks (NHB) (281 [4.9]). However, in males, IGF levels in NHWs (287 [3.6]) and NHBs (284 [4.3]) are similar and levels in Mexican-Americans are only moderately reduced (265 [3.4]). Notably, NHB’s have the highest molar ratio of IGF-I:IGFBP-3 at all ages. After adjustment for age and BMI, gender and race/ethnicity differences persist.
These cross-sectional data support exploration of the IGF axis as an explanation for some race/ethnic differences in cancer incidence.
PMCID: PMC2702997  PMID: 18812263
Cancer; Insulin-Like Growth Factor; Race/Ethnicity; Age
17.  Observational Epidemiologic Studies of Nutrition and Cancer: The Next Generation (with Better Observation) 
It would be of enormous public health importance if diet and physical activity—both modifiable behavioral factors--were causally related to cancer. Nevertheless, the nutritional epidemiology of cancer remains problematic, in part because of persistent concerns that standard questionnaires measure diet and physical activity with too much error. We present a new strategy for addressing this measurement error problem. First, as background, we note that food frequency and physical activity questionnaires require respondents to report ‘typical’ diet or activity over the previous year or longer. Multiple 24-hour recalls (24HR), based on reporting only the previous day’s behavior, offer potential cognitive advantages over the questionnaires, and biomarker evidence suggests the 24HR is more accurate than the food frequency questionnaire. The expense involved in administering multiple 24HRs in large epidemiologic studies, however, has up to now been prohibitive. In that context, we suggest that internet-based 24HRs, for both diet and physical activity, represent a practical and cost-effective approach for incorporating multiple recalls in large epidemiologic studies. We discuss 1) recent efforts to develop such internet-based instruments and their accompanying software support systems; 2) ongoing studies to evaluate the feasibility of using these new instruments in cohort studies; 3) additional investigations to gauge the accuracy of the internet-based recalls vis-à-vis standard instruments and biomarkers; and 4) new statistical approaches for combining the new instruments with standard assessment tools and biomarkers The incorporation of internet-based 24HRs into large epidemiologic studies may help advance our understanding of the nutritional determinants of cancer.
PMCID: PMC2688809  PMID: 19336550
Nutrition; Diet; Physical Activity; Cancer; Measurement error
18.  Ovarian Volumes Among Women with Endometrial Carcinoma: Associations with Risk Factors and Serum Hormones 
Gynecologic oncology  2007;107(3):431-435.
Data suggest that post-menopausal women with larger ovaries are at increased risk for endometrial carcinoma; however, analyses comparing ovarian volume to serum hormone levels are limited. Accordingly, we assessed ovarian volumes in relation to serum sex hormone levels among post-menopausal women with endometrial carcinoma who participated in a multi-center case control study.
Data for established risk and protective factors for endometrial carcinoma were collected via in-person interviews. Ovarian volumes were estimated from pathology reports. Associations between exposures and age-adjusted ovarian volumes were analyzed for 175 cases with available data. For a subset of 135 cases, we analyzed relationships between ovarian volume, adjusted for age and body mass index (BMI), and serum hormone levels by analysis of variance.
Ovarian volume declined progressively from 1.83 cm3 among women ages 55–59 years to 1.23 cm3 among women age 70 years or older (p-trend = 0.02). Larger ovarian volume was associated with early menarche (p-trend = 0.03), having given birth (p = 0.01), and weakly with elevated BMI (p- trend = 0.06). After adjustment, increased ovarian volume, was associated with higher estradiol (p - trend = 0.007); albumin-bound estradiol (p - trend = 0.01); and free estradiol (p - trend = 0.006) levels; androstenedione, estrone and estrone sulfate showed similar, though non-significant associations.
Among women with endometrial carcinoma, larger ovaries were associated with higher serum levels of estrogens. Further studies examining the role of the ovaries in post-menopausal hormonal carcinogenesis are warranted.
PMCID: PMC2831219  PMID: 17720234
Endometrial Carcinoma; Hormones; Ovary; Epidemiology
19.  Pregnancy weight gain is not associated with maternal or mixed umbilical cord estrogen and androgen concentrations 
Cancer causes & control : CCC  2008;20(2):263-267.
The association of maternal weight gain with serum hormone concentrations was explored in 75 women who had healthy, singleton pregnancies. Estradiol, estriol, estrone, androstenedione, testosterone, dehydroepiandrosterone (DHEA) and DHEA sulfate concentrations were measured both in maternal and mixed umbilical cord serum to assess hormone levels in both the maternal and fetal circulation at delivery. Our data show no association of maternal or cord steroid hormone concentrations with pregnancy weight gain. Increased exposure to steroid hormones, especially estrogens, during pregnancy has been hypothesized to play a role in subsequent breast cancer risk for both mother and female offspring. Our results are not consistent with an effect of pregnancy weight gain being mediated by this pathway as reflected by hormone concentrations at the end of pregnancy.
PMCID: PMC2631613  PMID: 18830676
Pregnancy; breast cancer; estrogens; androgens
20.  Can we use biomarkers in combination with self-reports to strengthen the analysis of nutritional epidemiologic studies? 
Identifying diet-disease relationships in nutritional cohort studies is plagued by the measurement error in self-reported intakes.
The authors propose using biomarkers known to be correlated with dietary intake, so as to strengthen analyses of diet-disease hypotheses. The authors consider combining self-reported intakes and biomarker levels using principal components, Howe's method, or a joint statistical test of effects in a bivariate model. They compared the statistical power of these methods with that of conventional univariate analyses of self-reported intake or of biomarker level. They used computer simulation of different disease risk models, with input parameters based on data from the literature on the relationship between lutein intake and age-related macular degeneration.
The results showed that if the dietary effect on disease was fully mediated through the biomarker level, then the univariate analysis of the biomarker was the most powerful approach. However, combination methods, particularly principal components and Howe's method, were not greatly inferior in this situation, and were as good as, or better than, univariate biomarker analysis if mediation was only partial or non-existent. In some circumstances sample size requirements were reduced to 20-50% of those required for conventional analyses of self-reported intake.
The authors conclude that (i) including biomarker data in addition to the usual dietary data in a cohort could greatly strengthen the investigation of diet-disease relationships, and (ii) when the extent of mediation through the biomarker is unknown, use of principal components or Howe's method appears a good strategy.
PMCID: PMC2841599  PMID: 20180978
21.  Methods of Epidemiology: Evaluating the Fat–Breast Cancer Hypothesis – Comparing Dietary Instruments and Other Developments 
Results from several large cohort studies that were reported 10 to 20 years ago seemed to indicate that the hypothesized link between dietary fat intake and breast cancer risk was illusory. In this article, we review several strands of more recent evidence that have emerged. These include two studies comparing the performance of dietary instruments used to investigate the dietary fat-breast cancer hypothesis, a large randomized disease prevention trial, a more recent meta-analysis of nutritional cohort studies, and a very large nutritional cohort study. Each of the studies discussed in this article suggests that a modest but real association between fat intake and breast cancer is likely. If the association is causative, it would have important implications for public health strategies in reducing breast cancer incidence. The evidence is not yet conclusive, but additional follow-up in the randomized trial, as well as efforts to improve dietary assessment methodology for cohort studies, may be sufficient to provide a convincing answer.
PMCID: PMC2496993  PMID: 18391610
breast cancer; dietary fat; dietary measurement error; food frequency questionnaire; multiple-day food record
22.  Poor Iron Status Is More Prevalent in Hispanic Than in Non-Hispanic White Older Adults in Massachusetts1 
The Journal of nutrition  2007;137(2):414-420.
Iron status and dietary correlates of iron status have not been well described in Hispanic older adults of Caribbean origin. The aim of this study was to evaluate iron status and describe dietary components and correlates of iron status in Hispanic older adults and in a neighborhood-based comparison group of non-Hispanic white older adults. Six hundred four Hispanic and non-Hispanic white adults (59-91 y of age) from the Massachusetts Hispanic Elders Study were included in the analysis. We examined physiological markers of iron status as well as dietary factors in relation to iron status. Dietary intake was assessed by FFQ. Our results revealed that Hispanics had significantly lower geometric mean serum ferritin (74.1 μg/L vs. 100 μg/L; P < 0.001), lower hemoglobin concentrations (137 ± 13 vs. 140 ± 12 g/L; P < 0.01), higher prevalence of anemia (11.5 vs. 7.3%; P < 0.05), and suboptimal hemoglobin concentrations (<125 g/L) for this age group (21.4 vs. 13.3%; P < 0.05). Iron deficiency anemia was higher (7.2% vs. 2.3%; P < 0.05) in Hispanic women. Hispanics had lower mean intakes of total iron, vitamin C, supplemental vitamin C, and total calcium than did non-Hispanic whites. After adjusting for age, sex, BMI, alcohol use, smoking, total energy intake, inflammation, diabetes, and liver disease, intake of heme iron from red meat was positively associated and dietary calcium was negatively associated with serum ferritin. This population of Hispanic older adults was significantly more likely than their non-Hispanic white neighbors to suffer from anemia and poor iron status, particularly among women. Cultural variation in dietary patterns may influence iron availability and body iron stores and contribute to an increased risk for iron deficiency anemia among some Hispanic older adults.
PMCID: PMC1857295  PMID: 17237320

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